Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis

Larkin, James; Chmielowski, Bartosz; Lao, Christopher D.; Hodi, F. Stephen; Sharfman, William H.; Weber, Jeffrey S.; Suijkerbuijk, Karijn P M; Azevedo, Sérgio Jobim; Li, Hewei; Reshef, Daniel S.; Avila, Alexandre; Reardon, David A.

doi:10.1634/theoncologist.2016-0487

Cited by 241 publications

(283 citation statements)

References 44 publications

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“…Interestingly, other cases of anti‐PD‐1‐associated encephalitis have been reported with preceding symptoms suspicious for infection, such as flu‐like symptoms or upper respiratory and sinus infection . Our case occurred approximately 10 weeks into therapy, consistent with other reports showing that neurologic toxicities arise at a median of 6–10 weeks into treatment .…”

Section: Discussionsupporting

confidence: 87%

Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy

et al. 2019

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Background Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life‐threatening immune‐related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies. Case Presentation We describe herein a patient with metastatic melanoma who developed epididymo‐orchitis followed by encephalitis while receiving pembrolizumab. The patient developed testicular pain and fever after his third dose of pembrolizumab; ultrasound evaluation demonstrated bilateral epididymo‐orchitis. He then developed headaches, fever, and altered mental status over the next week and was admitted to the hospital. Lumbar puncture revealed inflammatory changes consistent with meningoencephalitis; he did not improve with broad‐spectrum antibiotics, and an extensive workup for infectious etiologies, including cerebrospinal fluid testing using a clinical metagenomic next‐generation sequencing assay, was negative. He received high‐dose steroids for suspected autoimmune encephalitis, and both his orchitis and meningoencephalitis improved rapidly after one dose. He fully recovered after a 5‐week taper of oral steroids. Discussion Here, we report a case of epididymo‐orchitis complicating immune checkpoint inhibitor therapy. This patient subsequently developed severe encephalitis but rapidly improved with steroids. Clinicians should be aware of rare complications of these agents. Key Points Epididymo‐orchitis is a rare and potentially life‐threatening complication of anti‐programmed death protein 1 (anti‐PD‐1) therapy. For patients on anti‐PD‐1 therapy who develop either epididymo‐orchitis or epididymitis without clear infectious cause, immune‐related adverse events should be considered in the differential diagnosis. If severe, epididymo‐orchitis related to anti‐PD‐1 therapy may be treated with high‐dose corticosteroids.

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Section: Discussionsupporting

confidence: 87%

Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy

et al. 2019

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“…An analysis using a pharmacovigilance database reported an overall incidence of 0.93% of serious neurologic irAEs in patients who had melanoma who were treated with nivolumab with or without ipilimumab . The median time to onset was 45 days, and the time to resolution was 32 days.…”

Section: Checkpoint Inhibitorsmentioning

confidence: 99%

A review of cancer immunotherapy toxicity

Kennedy

Salama

2020

CA A Cancer J Clinicians

988

699

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Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicities often require specific management, which can include steroids and immune‐modulating therapy and for which consensus guidelines have been published. This review will focus on the toxicities of checkpoint inhibitors and chimeric antigen receptor T cells, including pathophysiology, diagnosis, and management.

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“…A review of the literature on leukoencephalopathy gave mixed results: while there are few published case reports linking mania directly with toxic leukoencephalopathy or immunotherapy, there are several papers strongly linking the genetic leukoencephalopathy CADASIL with bipolar affective disorder . Valenti and colleagues postulate that leukoencephalopathic pathology could cause affective changes via subcortical damage …”

Section: Discussionmentioning

confidence: 99%